1. Field of the Invention
The present disclosure in general relates to methods for treating neurodegenerative disorders. More particularly, the disclosure invention relates to methods for treating neurodegenerative disorders with an oral dosage formulation that contains both immediate-release and sustained-release drugs.
2. Description of Related Art
Neurodegenerative disorders are conditions in which cells of the brain and spinal cord are lost, which may eventually lead to central nervous system (CNS)-related dysfunction, which includes, for example, Alzheimer's disease, Parkinson's disease, Huntington's disease, etc.
Initial treatment for neurodegenerative disorders is dependent on diagnosis of the underlying condition. Currently, few therapies are available for the treatment of most neurodegenerative diseases. Therapy designed to enhance cholinergic function by inhibiting acetylcholinesterase (AChE) or by attenuating N-methyl-D-aspartate (NMDA) receptor function using 1-aminocyclohexane derivatives (e.g., memantine) has been adopted to stabilize cognitive function of the dementia patient. Recently, treatment with both 1-aminocyclohexane derivatives and acetylcholinesterase inhibitors (AChEI) have been hypothesized and demonstrated in U.S. Patent application No. 2009/0124659, which was filed by Moebius on Feb. 27, 2008. Moebius suggested that the novel combination of 1-aminocyclohexane derivatives and AChEI provides super additive effect to relieve the symptoms of dementia. The combination of drugs, are provided in one composition or in two different compositions for simultaneously or sequentially ingestion.
Current dose regimens for 1-aminocyclohexane derivatives and AChEI require patients to take more than one dose a day. This is undesirable for compliance decreases as the frequency of taking a drug increases. It also poses a difficulty for patients who start to lose cognitive function including memory to follow the dose regimens of drugs and thereby would further diminish the effects of treatment. Moreover, it is well known that certain medical conditions are most desirably treated with a dosage form that provides both immediate and extended therapeutic effects while reducing the number of doses necessary, thereby making therapy more convenient. Known examples of pharmaceutical formulations which provide both immediate and sustained-release of an active pharmaceutical ingredient may refer to U.S. Pat. No. 7,255,876 B2 to Shinoda et al. and U.S. Pat. No. 6,682,759 B2 to Lim et al. Therefore, there exists a need in this field a simple and convenient course of treatment for CNS-related dysfunction, such as dementia.
Our previous invention addressed such need by providing an improved oral formulation of the two drugs proposed by Moebius (Supra), i.e., 1-aminocyclohexane derivatives and AChEI. In the improved formulation, one drug is designed to be released immediately upon ingestion whereas the other is designed to be released over an extended period of time. With this proposed formulation, the course of treatment for CNS-related dysfunction such as dementia is greatly simplified by eliminating the need for a patient to take several pills either simultaneously or sequentially during the course of treatment, hence would greatly improve the effects of drugs in delaying and/or preventing the onset or progression of the disease.
However, 1-aminocyclohexane derivatives and AChEI are known to cause side effects such as dizziness, headache, fatigue, asthenia, somnolence, chills, insensible sweats, anorexia, gastrointestinal discomfort, nausea, and/or vomiting. As such, there is a need for unique formulation approaches that provide the desired therapeutic effects while minimizing the occurrence and/or severity of these and other undesired side effects.